title: Association of CYP2D6 metabolizer status with mammographic density change in response to tamoxifen treatment.
abstract: BACKGROUND
  Not all breast cancer patients respond to tamoxifen treatment, possibly due to genetic predisposition. As tamoxifen-induced reductions in percent mammographic density (PMD) have been linked to the risk and prognosis of breast cancer, we conducted a candidate gene study to investigate the association between germline CYP2D6 polymorphisms and PMD change.
  
  
  METHODS
  Baseline and follow-up mammograms were retrieved for 278 tamoxifen-treated subjects with CYP2D6 metabolizer status (extensive (EM), heterozygous extensive/intermediate (hetEM/IM) or poor metabolizer (PM)). Logistic regression analyses were conducted comparing subjects who experienced >10% reduction in PMD to those who experienced ≤10% reduction or increase.
  
  
  RESULTS
  After multivariate adjustment, PMD change was found to be significantly associated with the degree of CYP2D6 enzyme functionality (Ptrend = 0.021). Compared with EM, hetEM/IM and PM were 72% (95% confidence interval (CI): 0.10 to 0.79) and 71% (0.03 to 2.62) less likely to experience a >10% reduction, respectively.
  
  
  CONCLUSIONS
  Tamoxifen-induced change in PMD appears to have a genetic component.
authors.forename: Jingmei
authors.initials: J
authors.lastname: Li
authors.forename: Kamila
authors.initials: K
authors.lastname: Czene
authors.forename: Hiltrud
authors.initials: H
authors.lastname: Brauch
authors.forename: Werner
authors.initials: W
authors.lastname: Schroth
authors.forename: Pilar
authors.initials: P
authors.lastname: Saladores
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Keith
authors.initials: K
authors.lastname: Humphreys
authors.forename: Per
authors.initials: P
authors.lastname: Hall
mesh_terms: D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D000071060:Breast Density; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology* / Q000532:radiotherapy; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D042361:Mammary Glands, Human / Q000002:abnormalities*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D012307:Risk Factors; D013629:Tamoxifen / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D019389:Cytochrome P-450 CYP2D6